Using electron microscopy techniques, we propose to study the localization of structure of various differentiation-specific molecules, and the ultrastructure of the cells in which these molecules are found. New techniques for looking at the undersides of cells will be used to study the interactions between the extracellular matrix of cultured endothelial cells and the lower cell surface. The role of fibronectin, a major extracellular matrix formation will be examined. The structure of fibronectin will be further examined by rotary shadowing techniques. Alkaline phosphatase is a marker for certain tumor cells. The extracellular and intracellular localization of this enzyme will be examined in various human tumor cell lines. The murine teratocarcinoma system will be used to study gene expression. Shadowing techniques will be used to study new RNA molecules appearing after differentiation. Also, the formation of extracellular matrix and appearance of EGF receptors after differentiation will be studied. The information gained from these studies will provide a better understanding of the role of extracellular matrix formation and gene expression in malignancy.